Abstract
Background/Objectives: Lipid transfer protein (LTP) syndrome is a leading cause of primary food allergy in Mediterranean countries, often associated with severe reactions. Due to in vitro cross-reactivity among plant foods, clinical manifestations are unpredictable, frequently requiring multiple oral food challenges (OFC) to assess nut tolerance. These procedures increase healthcare burden and patient anxiety. This study evaluated the safety and utility of a mixed-nut oral food challenge (MixNut) in LTP-sensitized patients. Methods: In this prospective observational multi-center study, patients with LTP syndrome were enrolled. Group A included individuals allergic to fruits or vegetables who had avoided nuts; Group B included patients with suspected or confirmed nut allergy. Participants underwent a MixNut challenge comprising 2-4 nuts (≥3 g protein per nut). Results: Nineteen patients (73.7% male; median age 32.5 years) underwent MixNut, testing 52 individual nuts. All challenges were negative. The MixNut approach reduced the number of OFC by 63% (from 52 to 19) and total testing time from 208 to 76 h. Specific IgE levels to LTP allergens (Pru p 3, Cor a 8, Ara h 9) varied widely and did not predict clinical reactivity. Conclusions: MixNut is an efficient diagnostic tool for LTP syndrome, significantly reducing testing time, costs, and patient burden. It facilitates accurate dietary management and prevents unnecessary food avoidance. Further studies should optimize MixNut protocols and identify predictive markers for clinical reactivity.